1. Field of the Invention
This invention relates to a producing method of pheophorbide a which causes photosensitivity in human and animals and which is used in photoradiation therapy against cancer and the like.
2. Prior Art
Photoradiation therapy is used in diagnosis or therapy for inalignant tumors such as cancer. In this photoradiation therapy, a substance causing photosensitivity such as an organic pigment is selectively taken into tumor cells and is excited with low power level laser light irradiation so that the tumor cells can be killed. Theoretically, this photoradiation therapy has an advantage that only the tumor cells can be damaged due to the substance so that other normal cells are not damaged.
In the photoradiation therapy, the substance causing photosensitivity must have at least following conditions.
(1) It must have compatibility with the tumors. PA1 (2) It must have photochemical reactivity. PA1 (3) It must be able to be used in safety. (It must not have toxicity. It must be water-soluble and metabolic.) PA1 (4) It must not remain in the tumor cells more than a predetermined time. PA1 (5) It must be able to be produced repeatedly. PA1 (6) It must have operating experience in clinic. (It must show medical effects without any accident.) PA1 (a) The pheophorbide a is dissolved in dimethyl sulfoxide (DMSO) as an organic solvent. Then, this solution is diluted with a buffer solution of phosphoric acid so as to be used as the substance causing photosensitivity. PA1 (b) The powder of the pheophorbide a is kneaded with a small amount of alkali solution. Then, the resultant pheophorbide a in the form of paste is diluted with a buffer solution of phosphoric acid so as to be used as the substance causing photosensitivity. PA1 (c) The pheophorbide a is dissolved in albumin so as to be used as the substance causing photosensitivity. PA1 (d) The pheophorbide a is dissolved in lipidol (oil) so as to be used as the substance causing photosensitivity. PA1 (a) The organic solvent, DMSO is very poisonous. Thus, this process has a deficiency in safety. PA1 (b) After dilution, settlement is often caused, resulting in a deficiency in safety. PA1 (c) The albumin often causes anaphylaxis shock. Thus, this process has also a deficiency in safety. PA1 (d) Due to the character of the lipidol, it is impossible to use this substance in a vein. Accordingly, it can not be used for many kinds of therapy. PA1 dissolving sodium hydroxide in one solvent selected from n-propyl alcohol, isopropyl alcohol and the mixture of n-propyl alcohol and isopropyl alcohol so as to prepare a solution of the sodium hydroxide; PA1 dissolving the pheophorbide a into a solvent, which is miscible with the solvent selected from n-propyl alcohol, isopropyl alcohol and the mixture of n-propyl alcohol and isopropyl alcohol so as to prepare a solution of the pheophorbide a; and PA1 dissolving the solution of tile pheophorbide a in the solution of the sodium hydroxide so as to obtain sodium pheophorbide a.
It is well known that pheophorbide a can be used as the substance causing photosensitivity. The pheophorbide a satisfies the above mentioned conditions except safety (3). Precisely, the pheophorbide a is not water-soluble so as to be deposited in a human body. Thereby, shock accidents may be caused. Accordingly, it has been impossible to use the pheophorbide a for the human body as it is.
Therefore, it is an important subject to give water-solubility to the pheophorbide a. In the prior art, the following is processes have been used in order to achieve this subject.
However, the above processes have severe disadvantages respectively.